The serotonin-2C agonist Lorcaserin delays intravenous choice and modifies the subjective and cardiovascular effects of cocaine: A randomized, controlled human laboratory study.

Background: Lorcaserin is a modestly selective agonist for 2C serotonin receptors (5-HTR) approved for weight-loss therapy. This class can attenuate cue-induced responding and drug taking in preclinical studies, but effects in humans have not been reported.

Methods And Participants: We evaluated effects of single 10 mg doses of lorcaserin on the subjective and reinforcing effects of cocaine, using a randomized, double-blind, within-subject, cross-over design. Male, non-treatment-seeking, regular cocaine users received either single doses of oral placebo (n = 9) or lorcaserin (n = 9), followed by low- or high- doses of intravenous cocaine (0.23 or 0.46 mg/kg-injection). They were then allowed to self-administer the lower dose of cocaine.

Results: Cocaine was well tolerated after lorcaserin pretreatment. Oral lorcaserin did not modify the number of cocaine injections self-administered. However, it prolonged the time over which participants made intravenous choices relative to the duration of monetary (cash) decisions. Lorcaserin increased ratings of 'high' and 'stimulated' after low-dose cocaine or vehicle, but decreased craving for cocaine after intravenous vehicle. It also caused small but significant increases in heart rate following noncontingent injections of intravenous placebo or cocaine. When active cocaine was self-administered, lorcaserin decreased heart rate after selection of a monetary choice, but increased it following an intravenous choice.

Conclusions: Combined treatment with cocaine and lorcaserin was safe in a limited number of subjects, but did not diminish cocaine-motivated behavior or drug-induced 'high'. Some positive subjective effects of cocaine were enhanced by lorcaserin, and it delayed intravenous choices and decreased craving under some conditions. Effects on heart rate depended on the type of reinforcer being self-administered.

Trial Registration: clinicaltrials.gov Identifier, NCT02680288.